The continuing value of twin studies in the omics era

Dongen, Jenny van; Slagboom, P. Eline; Draisma, Harmen H.M.; Martin, Nicholas G.; Boomsma, Dorret I.

doi:10.1038/nrg3243

Cited by 327 publications

(276 citation statements)

References 150 publications

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“…In the young twin cohort, we have collected detailed phenotypic and genetic information for both the twin individuals and their parents, making it possible to establish an extension of the twin model (which incorporates data from twins and their parents) for genetic research. It is increasingly recognized that newly identified short nucleotide polymorphisms (SNPs) from traditional case-control GWASs only explain a small proportion of heritability in disease (van Dongen et al, 2012). By contrast, family-based association analysis (i.e., combining linkage and association analysis) based on the extended twin model offers a new analytic approach to identify cause of human variation.…”

Section: Genetic Research Using Family-based Association Analysismentioning

confidence: 99%

“…Given that monozygotic (MZ) twins are perfectly matched for age, sex, and genetic background, and partly for early environmental influences, the study of discordant MZ twins may offer novel insight into DNA variant, epigenetic variation and environmental effects associated with eye diseases and quantitative traits (van Dongen et al, 2012). We are working on epigenetic variation for myopia and glaucoma, and in the meantime, looking for funding and collaborators in this area.…”

Section: Discordant Twins Studymentioning

confidence: 99%

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The Guangzhou Twin Project: An Update

et al. 2012

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The Guangzhou Twin Registry is a population-based registry of twins residing in Guangzhou City. The initial registry database included 9,700 pairs of young twins recruited from the Official Household Registry of Guangzhou City. The registry is designed to provide a resource to identify the genetic and environmental causes of common diseases with an initial focus on eye diseases. From 2006 onward, phenotype and DNA collection have been completed for more than 1,200 twin pairs and their parents or siblings. Most of the young twins have come back for an annual examination of the progressive traits, such as refraction, ocular biometry, weight, and height. Genome-wide association scans have been completed recently. This article gives an update of the study design, cohort profile, previous findings, and future directions. Results from the Guangzhou Twin Project may contribute to the understanding of gene-environmental interplay for complex diseases in both adults and children.

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Section: Genetic Research Using Family-based Association Analysismentioning

confidence: 99%

Section: Discordant Twins Studymentioning

confidence: 99%

The Guangzhou Twin Project: An Update

et al. 2012

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“…Numerous studies have shown a wide variation in heritability of age-related phenotypes (Steves et al, 2012), but little is known about the extent of shared genetic effects on different systems. Similarly, the degree to which environmental factors impact upon aging trends in various body systems is unknown.Twin studies can investigate the causes of variation in a population (van Dongen et al, 2012). Identical (MZ) twins share virtually all of their variable DNA sequence, while non-identical (DZ) twins share on average only half of their segregating genes.…”

mentioning

confidence: 99%

“…Twin studies can investigate the causes of variation in a population (van Dongen et al, 2012). Identical (MZ) twins share virtually all of their variable DNA sequence, while non-identical (DZ) twins share on average only half of their segregating genes.…”

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confidence: 99%

Aging Trajectories in Different Body Systems Share Common Environmental Etiology: The Healthy Aging Twin Study (HATS)

et al. 2016

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Little is known about the extent to which aging trajectories of different body systems share common sources of variance. We here present a large twin study investigating the trajectories of change in five systems: cardiovascular, respiratory, skeletal, morphometric, and metabolic. Longitudinal clinical data were collected on 3,508 female twins in the TwinsUK registry (complete pairs:740 monozygotic (MZ), 986 dizygotic (DZ), mean age at entry 48.9 ± 10.4, range 18-75 years; mean follow-up 10.2 ± 2.8 years, range 4-17.8 years). Panel data on multiple age-related variables were used to estimate biological ages for each individual at each time point, in linear mixed effects models. A weighted average approach was used to combine variables within predefined body system groups. Aging trajectories for each system in each individual were then constructed using linear modeling. Multivariate structural equation modeling of these aging trajectories showed low genetic effects (heritability), ranging from 2% in metabolic aging to 22% in cardiovascular aging. However, we found a significant effect of shared environmental factors on the variations in aging trajectories in cardiovascular (54%), skeletal (34%), morphometric (53%), and metabolic systems (53%). The remainder was due to environmental factors unique to each individual plus error. Multivariate Cholesky decomposition showed that among aging trajectories for various body systems there were significant and substantial correlations between the unique environmental latent factors as well as shared environmental factors. However, there was no evidence for a single common factor for aging. This study, the first of its kind in aging, suggests that diverse organ systems share non-genetic sources of variance for aging trajectories. Confirmatory studies are needed using population-based twin cohorts and alternative methods of handling missing data.Keywords: aging, longitudinal studies, multi-morbidities, twin studies, multi-system changes An important question facing researchers in the field of aging is to what extent the causes of age-related decline in one trait are shared with other aging phenotypes. Clinicians observe that not all body systems change at the same rate within an individual. Numerous studies have shown a wide variation in heritability of age-related phenotypes (Steves et al., 2012), but little is known about the extent of shared genetic effects on different systems. Similarly, the degree to which environmental factors impact upon aging trends in various body systems is unknown.Twin studies can investigate the causes of variation in a population (van Dongen et al., 2012). Identical (MZ) twins share virtually all of their variable DNA sequence, while non-identical (DZ) twins share on average only half of their segregating genes. Classical twin studies compare the variability in MZ pairs compared with DZ pairs and estimate the extent attributable to genetic factors (the heritability) and to environmental factors either shared by the twin pair or unique to each tw...

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“…However, it is also well known from epidemiological studies that certain environmental factors have a strong influence on cancer risk, for example tobacco smoking and UV sunlight exposure. In order to quantify this nongenetic effect, the unique power of human twin studies has been fundamental [6].…”

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confidence: 99%

Using epigenomic studies in monozygotic twins to improve our understanding of cancer

2014

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Cancer is a set of diseases that exhibit not only genetic mutations but also a profoundly distorted epigenetic landscape. Over the last two decades, great advances have been made in identifying these alterations and their importance in the initiation and progression of cancer. Epigenetic changes can be seen from the very early stages in tumorigenesis and dysregulation of the epigenome has an increasingly acknowledged pathogenic role. Epigenomic twin studies have great potential to contribute to our understanding of complex diseases, such as cancer. This is because the use of monozygotic twins discordant for cancer enables epigenetic variation analysis without the confounding influence of the constitutive genetic background, age or cohort effects. It therefore allows the identification of susceptibility loci that may be sensitive to modification by the environment. These studies into cancer etiology will potentially lead to robust epigenetic markers for the detection and risk assessment of cancer.

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The continuing value of twin studies in the omics era

Cited by 327 publications

References 150 publications

The Guangzhou Twin Project: An Update

The Guangzhou Twin Project: An Update

Aging Trajectories in Different Body Systems Share Common Environmental Etiology: The Healthy Aging Twin Study (HATS)

Using epigenomic studies in monozygotic twins to improve our understanding of cancer

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